Recently, cancer stem cells have been attracting attention in the field of cancer therapy and research. These cancer stem cells are said to be a cause that induces resistance against therapy or recurrence/metastasis of cancer.
An adhesion molecule CD44 of which ligand is hyaluronic acid and which is expressed in the cell membrane in cancer stem cells is a cancer stem cell marker and involved in their properties as cancer stem cells.
CD44 gene comprises 20 exons and produces various variant isoforms through alternative splicing (FIG. 1). It is believed that CD44 variant isoforms (especially, CD44v8-10 comprising variant exons 8, 9 and 10) that are produced from CD44 variant mRNAs bind to cystine transporter xCT in the cell membrane, promote cystine uptake and increase the level of intracellular glutathione (antioxidant), thereby enhancing the resistance against oxidation stress of anticancer agents and radiation (FIG. 2). Insertion of these variant exons is not caused by abnormalities in the genomic sequence but caused by abnormalities in a certain splice regulator specific to cancer stem cells (Non-Patent Document No. 1).